The effect of solid food diet therapies on the induction and maintenance of remission in Crohn's disease: a systematic review.

BACKGROUND: The efficacy of highly restrictive dietary therapies such as exclusive enteral nutrition (EEN) in the induction of remission in Crohn's disease (CD) are well established, however, ongoing issues exist with its poor palatability, restrictions, and adherence. The primary aim of this review is to evaluate the current evidence for the efficacy of exclusively solid food diets on the induction and maintenance of clinical and biochemical remission in CD. Secondary aims include impact on endoscopic healing and quality of life. METHODS: A systematic review of all randomised controlled trials (RCTs), open-label randomised trials and head-to-head clinical trials assessing solid food diet intervention in patients with active or inactive Crohn's disease was conducted. Studies included adult and paediatric patients with a verified disease activity index at baseline and follow up (Harvey Bradshaw Index, HBI; Crohn's disease activity index, CDAI and paediatric CDAI, PCDAI). Additional secondary endpoints varied between studies, including endoscopic and biochemical responses, as well as quality of life measures. Two authors independently performed critical appraisals of the studies, including study selection and risk of bias assessments. RESULTS: 14 studies were included for review, with several studies suggesting clinically significant findings. Clinical remission was achieved in a paediatric population undertaking the Mediterranean diet (MD) (moderate risk of bias). In adults, the Crohn's disease exclusion diet (CDED) was comparable to the CDED with partial enteral nutrition (PEN) diet in induction of remission (moderate risk of bias). A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet was also shown to decrease symptoms in patients with quiescent or mildly active CD (high risk of bias), however, this was not corroborated by other low FODMAP diet studies. CONCLUSIONS: There are promising outcomes for the MD and CDED in inducing clinical remission in mild to moderate CD. The results need to be interpreted with caution due to design limitations, including issues with combining outcomes among CD and UC patients, and small sample size. The current evidence for solid food dietary therapy in CD is limited by the lack of high quality studies and moderate to high bias. Future well designed studies are needed to confirm their efficacy.

A real-life pediatric experience of Crohn's disease exclusion diet at disease onset and in refractory patients.

OBJECTIVES: We aimed to appraise the real-life efficacy of Crohn's disease exclusion diet (CDED) coupled with partial enteral nutrition (PEN) in inducing clinical and biochemical remission at disease onset and in patients with loss of response to biologics and immunomodulators. METHODS: We retrospectively gathered data of patients aged less than 18 years of age with a diagnosis of Crohn's disease (CD), who received CDED coupled with PEN at a tertiary level pediatric inflammatory bowel disease center. RESULTS: Sixty-six patients were identified. Forty (60.6%) started CDED plus PEN at disease onset and 26 (39.4%) received CDED with PEN as add-on therapy. Forty-six (69.7%) patients achieved clinical remission (weighted Pediatric Crohn's Disease Activity Index < 12.5) at the end of phase 1, 44 (66.7%) normalized c-reactive protein levels (<0.5 mg/dL) and 18 (27.2%) patients normalized calprotectin levels (<150 µg/g). Nine of 19 (47.3%) of patients with clinically severe disease (defined by Physician Global Assessment) achieved clinical remission at the end of phase I. Patients with extraintestinal manifestations had statistically lower clinical response rates to the dietary regimen (p = 0.018). Among patients who received CDED + PEN as add-on treatment, a previous successful course of Exclusive Enteral Nutrition was associated with statistically higher clinical remission rates at Week 8 (p = 0.026). Clinical response at Week 4 was an independent predictor of clinical remission and fecal calprotectin normalization at Week 8 (p = 0.002). CONCLUSION: CDED with PEN confirmed its efficacy in a real-life setting, proving to be effective also in refractory patients and those with severe disease. Early clinical response predicts clinical remission at the end of phase 1.

Formula modifications to the Crohn's disease exclusion diet do not impact therapy success in paediatric Crohn's disease.

OBJECTIVES: The Crohn's disease exclusion diet (CDED) + partial enteral nutrition (PEN) is an emerging diet used to induce clinical remission in children with active Crohn's disease (CD). This study aims to determine the effectiveness of using the CDED+PEN to induce clinical remission in an Australian group of children with active CD using different PEN formulas and incorporating patient dietary requirements. METHODS: We retrospectively collected data from children (both newly diagnosed and with existing CD while on therapy) with active CD (Paediatric Crohn's Disease Activity Index [PCDAI] ≥10) and biochemical evidence of active disease (elevated C-reactive protein [CRP], erythrocyte sedimentation rate [ESR] or faecal calprotectin [FC]) who completed at least phase 1 (6 weeks) of the CDED+PEN to induce clinical remission. Data were collected at baseline, Week 6 and Week 12. The primary endpoint was clinical remission at Week 6 defined as PCDAI < 10. RESULTS: Twenty-four children were included in phase 1 analysis (mean age 13.8 ± 3.2 years). Clinical remission at Week 6 was achieved in 17/24 (70.8%) patients. Mean PCDAI, CRP, ESR and FC decreased significantly after 6 weeks (p < 0.05). Formula type (cow's milk based, rice based, soy based) did not affect treatment efficacy. A greater than 50% decrease in FC was achieved in 14/21 (66.7%) patients who completed phase 1 and 12/14 (85.7%) patients who completed phase 2 of the CDED+PEN. CONCLUSIONS: Formula modifications to the CDED+PEN do not impact the expected treatment efficacy in Australian children with active luminal CD.

Reverse-engineered exclusive enteral nutrition in pediatric Crohn's disease: A pilot trial.

BACKGROUND: In pediatric Crohn's disease (CD), commercial formulas used as exclusive enteral nutrition (EEN) are effective at inducing remission. This study aims to assess the impact of a whole-food blended smoothie as EEN on CD activity and the intestinal microbiome. METHODS: A 4-week prospective trial assessed the impact of EEN with a whole-food smoothie on newly diagnosed mild-to-moderate active pediatric CD. The smoothie with a multivitamin were developed to meet age-appropriate nutritional requirements. Assessment over 4 weeks included Pediatric Crohn's Disease Activity Index (PCDAI), serum laboratories, fecal calprotectin (FCP), and stool collection for metagenomic shotgun sequencing and microbiota composition analysis. Clinical remission was defined as PCDAI ≤ 10 at week 4. RESULTS: Ten participants were enrolled with median age 14.5 years, and 8 completed the trial. Baseline mean PCDAI was 26.3 ± 9.1 and mean FCP 1149 ± 718 µg/g. At week 4, 80% of participants achieved clinical remission. FCP decreased by over half in 60% of participants, with FCP below 250 µg/g in 60% and below 100 µg/g in 40%. Microbiome analysis showed a significant increase in species richness over 4 weeks (p = 0.01). Compared to baseline, the relative abundance at week 2 and at week 4 was significantly increased for Bifidobacterium and Streptococcus and decreased for Blautia (p < 0.05 for all). CONCLUSION: A whole-food blended smoothie was effective for inducing clinical remission and decreasing FCP in pediatric CD similar to commercial EEN formulas. Further research may give insight into data-driven whole-food dietary approaches for CD management. CLINICALTRIALS: gov NCT03508193.

Co-Development of Three Dietary Indices to Facilitate Dietary Intake Assessment of Pediatric Crohn's Disease Patients.

Literature on dietary behaviours of the pediatric Crohn's Disease (CD) population and the relationship between dietary intake and CD activity is limited. Three dietary indices were developed and tested to conduct dietary pattern analysis in pediatric patients with CD consuming a free diet following remission induction via exclusive enteral nutrition (n = 11). Index scores underwent descriptive and inferential analysis. The mean adjusted scores (out of 100) for the Pediatric Western Diet Index, Pediatric Prudent Diet Index, and Pediatric-Adapted 2010 Alternate Healthy Eating Index (PA2010-AHEI) were 29.82 ± 15.22, 34.25 ± 15.18, and 51.50 ± 11.69, respectively. The mean Western-to-Prudent ratio was 0.94 ± 0.55. A significant correlation (r = -0.71) and relationship (F[1, 9] = 9.04, P < 0.05, R2 = 0.501) between the Western-to-Prudent ratio and PA2010-AHEI was found. The results suggest participants were not following a Western or Prudent diet, and were consuming foods not captured by the indices. More research is needed to describe dietary intake of individuals with CD, validate dietary indices in diverse samples, and explore the utility of these indices in CD assessment and treatment. The co-authors hope this work will stimulate/inspire subsequent interprofessional, dietitian-led research on this topic.

The Relationship of Adherence to the Mediterranean Diet with Disease Activity and Quality of Life in Crohn's Disease Patients.

Background and Objectives: Emerging evidence is placing the Mediterranean diet (MD) in the spotlight as a potential dietary model that could benefit inflammatory bowel disease (IBD) patients in terms of prevention and progress of the disease. The main aim of the present study is to shed some light on the relationship between the adherence to the MD and the degree of disease activity, as well as the quality of life in patients with Crohn's disease (CD). Materials and Methods: An administered questionnaire was used to assess and record a number of parameters, including recent medical and weight history, anthropometric characteristics, disease activity (in remission or active disease), and quality of life of both male and female CD patients. Moreover, the level of compliance of the participants to the Mediterranean diet model was evaluated and its relationship with disease activity and quality of life was investigated. Results: Adherence to the MD was significantly higher in patients with inactive disease than in those with active disease (p = 0.019). According to the correlation analysis conducted, adherence to the MD was negatively correlated with disease activity (p = 0.039) and positively correlated with quality of life (QoL) (p = 0.046) of the participants. Intake of fruits, vegetables, and dairy products was significantly higher in remission patients (p = 0.046, p = 0.001, p = 0.041, respectively). Conclusions: We conclude, according to the findings of the study, that adherence to the MD is associated with disease activity and QoL in patients with CD. Future research should focus on MD intervention studies on IBD patients in order to assess its effect on modulating disease activity/course and related inflammatory biomarkers.

A Randomized Trial Comparing the Specific Carbohydrate Diet to a Mediterranean Diet in Adults With Crohn's Disease.

BACKGROUND & AIMS: This study compared the effectiveness of the Specific Carbohydrate Diet (SCD) to the Mediterranean diet (MD) as treatment for Crohn's disease (CD) with mild to moderate symptoms. METHODS: Adult patients with CD and with mild-to-moderate symptoms were randomly assigned 1:1 to consume the MD or SCD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks according to their assigned diet. After 6 weeks, participants were instructed to follow the diet independently. The primary outcome was symptomatic remission at week 6. Key secondary outcomes at week 6 included fecal calprotectin (FC) response (FC <250 µg/g and reduction by >50% among those with baseline FC >250 µg/g) and C-reactive protein (CRP) response (high-sensitivity CRP <5 mg/L and >50% reduction from baseline among those with high-sensitivity CRP >5 mg/L). RESULTS: The study randomized 194 patients, and 191 were included in the efficacy analyses. The percentage of participants who achieved symptomatic remission at week 6 was not superior with the SCD (SCD, 46.5%; MD, 43.5%; P = .77). FC response was achieved in 8 of 23 participants (34.8%) with the SCD and in 4 of 13 participants (30.8%) with the MD (P = .83). CRP response was achieved in 2 of 37 participants (5.4%) with the SCD and in 1 of 28 participants (3.6%) with the MD (P = .68). CONCLUSIONS: The SCD was not superior to the MD to achieve symptomatic remission, FC response, and CRP response. CRP response was uncommon. Given these results, the greater ease of following the MD and other health benefits associated with the MD, the MD may be preferred to the SCD for most patients with CD with mild to moderate symptoms. ClinicalTrials.gov Identifier: NCT03058679.

Personalized Research on Diet in Ulcerative Colitis and Crohn's Disease: A Series of N-of-1 Diet Trials.

INTRODUCTION: Evidence about specific carbohydrate diet (SCD) for inflammatory bowel disease (IBD) is limited. We conducted 54 single-subject, double-crossover N-of-1 trials comparing SCD with a modified SCD (MSCD) and comparing each with the participant's baseline, usual diet (UD). METHODS: Across 19 sites, we recruited patients aged 7-18 years with IBD and active inflammation. Following a 2-week baseline (UD), patients were randomized to 1 of 2 sequences of 4 alternating 8-week SCD and MSCD periods. Outcomes included fecal calprotectin and patient-reported symptoms. We report posterior probabilities from Bayesian models comparing diets. RESULTS: Twenty-one (39%) participants completed the trial, 9 (17%) completed a single crossover, and 24 (44%) withdrew. Withdrawal or early completion occurred commonly (lack of response [n = 11], adverse events [n = 11], and not desiring to continue [n = 6]). SCD and MSCD performed similarly for most individuals. On average, there was <1% probability of a clinically meaningful difference in IBD symptoms between SCD and MSCD. The average treatment difference was -0.3 (95% credible interval -1.2, 0.75). There was no significant difference in the ratio of fecal calprotectin geometric means comparing SCD and MSCD (0.77, 95% credible interval 0.51, 1.10). Some individuals had improvement in symptoms and fecal calprotectin compared with their UD, whereas others did not. DISCUSSION: SCD and MSCD did not consistently improve symptoms or inflammation, although some individuals may have benefited. However, there are inherent difficulties in examining dietary changes that complicate study design and ultimately conclusions regarding effectiveness.

The Impact of Compliance During Exclusive Enteral Nutrition on Faecal Calprotectin in Children With Crohn Disease.

ABSTRACT: It remains unclear whether suboptimal response to exclusive enteral nutrition (EEN) in some children with Crohn disease (CD) is explained by poor compliance. The present study measured faecal gluten immunogenic peptides (GIP), a biomarker of gluten intake, in 45 children (3- 17 years) with CD, and explored associations with faecal calprotectin (FC) levels at 33 and 54 days of EEN. FC decreased in patients with undetectable GIP at both 33 and 54 days of EEN (mean decrease, 33 days: -743 mg/kg, 54 days: -1043 mg/kg, P  < 0.001) but not in patients who had detectable levels. At EEN completion, patients with undetectable GIP had a lower FC by 717 mg/kg compared with patients with a positive GIP result (P = 0.042) and demonstrated a greater decline from baseline FC (-69% vs +5%, P = 0.011). Poorer response to EEN is explained in part by diminished compliance. Faecal GIP might be useful as proxy biomarker of EEN compliance.

The effects of probiotics, prebiotics and synbiotics on the reduction of IBD complications, a periodic review during 2009-2020.

AIMS: To perform a systematic review on randomized controlled trials to examine the efficacy of probiotics, prebiotics and synbiotics in the treatment of IBD. METHODS AND RESULTS: PubMed, Web of science, Scopus and Google Scholar were systematically searched from January 2009 to January 2020 using the following keywords: 'Inflammatory Bowel Disease', 'Probiotics' and 'Clinical trial'. The statistical analysis was performed using SPSS software version 24.0. A total of 1832 articles were found during the initial search and 21 clinical trials were eligible. Studies comparing the effects of probiotics and placebo among patients with active ulcerative colitis (UC) showed a significant difference in clinical outcomes. Moreover, probiotics improved the overall induction of remission rates among patients with Crohn's disease (CD). Probiotics significantly decreased the IL-1ß, TNF-α and IL-8 levels. Also, the need for systemic steroids, hospitalization, surgery, as well as histological score and disease activity index significantly decreased in patients who used probiotic or pro-/synbiotics. CONCLUSIONS: The use of probiotics, as food supplements, can induce anti-inflammatory reactions, balance the intestinal homeostasis and induce remission in IBD. The efficacy of probiotics on remission induction is more reported in UC rather than CD. Larger well-designed clinical trials are needed to further determine whether probiotics are of clear benefits for remission in IBD.

Elemental diet therapy plays a significant role in preventing surgical recurrence of Crohn's disease in the era of biologics.

PURPOSE: Most patients with Crohn's disease (CD) experience surgical recurrence. In this era of novel therapies, we conducted this study to clarify which treatments effectively decrease the risk of surgical recurrence in patients with CD. METHODS: The subjects of this retrospective study were 37 patients with CD. We created cumulative surgery rate curves and performed univariate and multivariate analyses. RESULTS: Univariate analysis revealed that patients who consumed an elemental diet (ED; ≥ 900 kcal/day), anti-tumor necrosis factor-alpha, and thiopurines had a significantly better prognosis than those who did not (p = 0.011, p = 0.025, and p = 0.0080, respectively). Multivariate analysis revealed that ED therapy and thiopurines were independent significant factors for controlling surgical recurrence (p = 0.046 and p = 0.032, respectively). Additional analyses showed that the most promising ED therapeutic dose was ≥ 1200 kcal/day, while an ED therapeutic dose of ≥ 900 kcal/day was acceptable. CONCLUSIONS: Although univariate analyses revealed that all three treatment strategies had significant effects on surgical recurrence in patients with CD, multivariate analysis revealed that only ED therapy was significantly associated with surgical recurrence rates. Thus, ED therapy plays an important role in the management of CD, even in the era of biological therapies.

Adherence to a Mediterranean diet is associated with a lower risk of later-onset Crohn's disease: results from two large prospective cohort studies.

OBJECTIVE: To examine the relationship between Mediterranean diet and risk of later-onset Crohn's disease (CD) or ulcerative colitis (UC). DESIGN: We conducted a prospective cohort study of 83 147 participants (age range: 45-79 years) enrolled in the Cohort of Swedish Men and Swedish Mammography Cohort. A validated food frequency questionnaire was used to calculate an adherence score to a modified Mediterranean diet (mMED) at baseline in 1997. Incident diagnoses of CD and UC were ascertained from the Swedish Patient Register. We used Cox proportional hazards modelling to calculate HRs and 95% CI. RESULTS: Through December of 2017, we confirmed 164 incident cases of CD and 395 incident cases of UC with an average follow-up of 17 years. Higher mMED score was associated with a lower risk of CD (Ptrend=0.03) but not UC (Ptrend=0.61). Compared with participants in the lowest category of mMED score (0-2), there was a statistically significant lower risk of CD (HR=0.42, 95% CI 0.22 to 0.80) but not UC (HR=1.08, 95% CI 0.74 to 1.58). These associations were not modified by age, sex, education level, body mass index or smoking (all Pinteraction >0.30). The prevalence of poor adherence to a Mediterranean diet (mMED score=0-2) was 27% in our cohorts, conferring a population attributable risk of 12% for later-onset CD. CONCLUSION: In two prospective studies, greater adherence to a Mediterranean diet was associated with a significantly lower risk of later-onset CD.

A Diet Low in Red and Processed Meat Does Not Reduce Rate of Crohn's Disease Flares.

BACKGROUND & AIMS: Diet may be an important factor in the progression of Crohn's disease (CD). We performed a randomized controlled trial to determine whether reduced consumption of red and processed meats decreases the risk of symptomatic relapse of CD, analyzing results from the Food and Crohn's Disease Exacerbation Study (FACES) trial. METHODS: Adults with CD were recruited into the FACES trial from IBD Partners, an Internet-based cohort of patients with inflammatory bowel disease, from November 2013 through June 2015. Individuals who were in remission (CD activity index [sCDAI] scores of ≤150), had completed a biannual survey, and reported consumption of red meat at least once weekly were randomly assigned to groups that consumed a minimum of 2 servings/week of red or processed meat (high meat, n = 118) or not more than 1 serving per month (low meat, n = 96) for 49 weeks. The primary outcome was relapse of CD, defined as increase in sCDAI score by ≥70 points and to >150 or a need for CD surgery or new CD medication. A secondary outcome, moderate or severe relapse, was based on an increase in sCDAI to >219. RESULTS: During the trial, the high-meat groups reported consumption of 2 or more servings of red or processed meat during 98.5% of observed weeks compared with 18.8% of weeks for the low-meat group. Any and moderate to severe relapse occurred in 62% of participants in the high-meat group and 42% of participants in the low-meat group. There were no significant differences in time to any (P = .61) or moderate/severe (P = .50) relapse. CONCLUSIONS: In an analysis of data from the FACES trial, we found that among patients with CD in remission, level of red and processed meat consumption was not associated with time to symptomatic relapse. ClinicalTrials.gov, Number: NCT0192673.

Treatment of Active Crohn's Disease With an Ordinary Food-based Diet That Replicates Exclusive Enteral Nutrition.

BACKGROUND & AIMS: Exclusive enteral nutrition (EEN) is the only established dietary treatment for Crohn's disease (CD), but its acceptability is limited. There is a need for novel dietary treatments for CD. METHODS: We evaluated the effects of an individualized food-based diet (CD-TREAT), with similar composition to EEN, on the gut microbiome, inflammation, and clinical response in a rat model, healthy adults, and children with relapsing CD. Twenty-five healthy adults randomly received EEN or CD-TREAT for 7 days, followed by a 14-day washout period, followed by the alternate diet. Fecal microbiome and metabolome were assessed before and after each diet. HLA-B7 and HLA-B27 transgenic rats with gut inflammation received EEN, CD-TREAT, or standard chow for 4 weeks. Fecal, luminal, and tissue microbiome, fecal metabolites, and gut inflammation were assessed. Five children with active CD activity received CD-TREAT and their clinical activity and calprotectin were evaluated after 8 weeks of treatment. RESULTS: For healthy adults, CD-TREAT was easier to comply with and more acceptable than EEN. CD-TREAT induced similar effects to EEN (EEN vs CD-TREAT) on fecal microbiome composition, metabolome, mean total sulfide (increase 133.0 ± 80.5 vs 54.3 ± 47.0 nmol/g), pH (increase 1.3 ± 0.5 vs 0.9 ± 0.6), and the short-chain fatty acids (µmol/g) acetate (decrease 27.4 ± 22.6 vs 21.6 ± 20.4), propionate (decrease 5.7 ± 7.8 vs 5.2 ± 7.9), and butyrate (decrease 7.0 ± 7.4 vs 10.2 ± 8.5). In the rat model, CD-TREAT and EEN produced similar changes in bacterial load (decrease 0.3 ± 0.3 log10 16S rRNA gene copies per gram), short-chain fatty acids, microbiome, and ileitis severity (mean histopathology score decreases of 1.25 for EEN [P = .015] and 1.0 for CD-TREAT [P = .044] vs chow). In children receiving CD-TREAT, 4 (80%) had a clinical response and 3 (60%) entered remission, with significant concurrent decreases in fecal calprotectin (mean decrease 918 ± 555 mg/kg; P = .002). CONCLUSION: CD-TREAT replicates EEN changes in the microbiome, decreases gut inflammation, is well tolerated, and is potentially effective in patients with active CD. ClinicalTrials.gov, numbers NCT02426567 and NCT03171246.

Adherence to Mediterranean diet in Crohn's disease.

PURPOSE: To assess the adherence to MD in patients with Crohn's disease (CD). METHODS: Outpatients with CD were enrolled in this protocol. Medical history, disease activity, dietary intake, habitual Mediterranean diet (MedDiet) score, anthropometric measurements and Inflammatory Bowel Disease Questionnaire (IBDQ) were recorded. Blood samples were collected for quantification of biochemical and inflammatory indices. RESULTS: A total of 86 patients with CD were enrolled: 41 in relapse (5 ≤ Harvey Bradshaw Index ≤ 14) and 45 in remission (Harvey Bradshaw Index ≤ 4). Adherence to MD was greater in patients with inactive disease. The MedDiet score correlated positively with the IBDQ (p = 0.008) and negatively with disease activity (p < 0.001). CONCLUSIONS: Adherence to Mediterranean diet is associated with improved quality of life in CD patients. Higher adherence to Mediterranean diet could be of importance in patients with CD to improve quality of life and reduce disease activity.

Partial enteral nutrition induces clinical and endoscopic remission in active pediatric Crohn's disease: results of a prospective cohort study.

The aim of this study was to evaluate rates of clinical remission, endoscopic remission, and mucosal healing after a 6-week treatment period with partial enteral nutrition (PEN) and to compare them to those obtained by standard exclusive enteral nutrition (EEN) treatment in children with active Crohn's disease (CD). Twenty-five patients with active CD (median age 13.6 years, range 3.6-18.0) were recruited to either PEN (n = 12) or EEN (n = 13) treatment groups. The PEN group received 75% of their dietary needs from a polymeric formula plus one meal per day from an anti-inflammatory diet (AID). Patients were assessed at weeks 0, 1, 3, and 6 using clinical and laboratory parameters. Endoscopic assessment was performed at induction and week 6. On intention to treat analysis, clinical remission (Pediatric CD Activity Index < 10) was achieved in 69.2% and 75.0% of EEN and PEN patients, respectively (p = 0.999). The endoscopic remission (Simple Endoscopic Score for CD (SES-CD) ≤ 2) rates were 45.5% in both groups, while mucosal healing rates (SES-CD = 0) were 45.5% with EEN and 27.3% with PEN (p = 0.659).Conclusion: The results of our prospective pilot study suggest that PEN, allowing one meal from AID, could be as effective as EEN in inducing clinical and endoscopic remission in children with active CD. However, larger randomized controlled studies are warranted to confirm our findings.Trial registration: This clinical trial was registered under the number ClinicalTrials.govidentifier: NCT03176875.What is Known:• Exclusive enteral nutrition is a first-line treatment in active pediatric Crohn's disease; however, patients often find it difficult to adhere to.• Exclusive enteral nutrition is more effective than corticosteroids in achieving mucosal healing.What is New:• This is the first prospective study on partial enteral nutrition in active pediatric Crohn's disease, evaluating not only clinical, but also endoscopic remission.• A novel approach of partial enteral nutrition that allows one meal per day from an anti-inflammatory diet was as effective as exclusive enteral nutrition in inducing clinical and endoscopic remission in active Crohn's disease.

[Crohn's Disease Exclusion Diet - an alternative to exlusive enteral nutritional therapy in children and adolescents with Crohn's disease? Statement of the GPGE working groups CEDATA and Nutrition/Nutrition Medicine]. / Crohnʼs Disease Exclusion Diet (CDED) als Alternative zur exklusiven Ernährungstherapie bei Kindern und Jugendlichen mit Morbus Crohn? Stellungnahme der Arbeitsgemeinschaften CEDATA und Ernährung/Diätetik/Ernährungsmedizin der Gesellschaft für pädiatrische Gastroenterologie und Ernährung e. V.

Epidemiological an clinical observations as well as results from animal studies indicate that nutrition can play a role in the development of inflammatory bowel disease (IBD). Exclusive enteral nutrition therapy represents an example for modulating inflammatory responses solely through diet modification. Therefore, caretakers, patients, families, doctors and nutritionists seek for more dietary options to control IBD. These options include partial enteral nutrition therapy as for example the socalled Crohn's disease exclusion diet. The following statement summarizes existing data and provides recommendations for the current management of enteral nutrition therapy in pediatric Crohn's disease.

Nutritional regulators of intestinal inflammation.

PURPOSE OF REVIEW: Recent knowledge teaches us that food is one of the most important environmental factors affecting our health from disease prevention to cause. Food is one of the key players in the normal gut microenvironment, affecting microbial composition, function, gut barrier and host immunity. This review aims to summarize the current data on food components as regulators of intestinal inflammation, with particular focus on the inflammatory bowel diseases (IBDs). RECENT FINDINGS: We summarize our current understanding on nutrition as possible cause and treatment for IBD and concentrate on several food components that have an anti-inflammatory role on the intestine (vitamin D, butyrate, resveratrol, curcumin). SUMMARY: The proven efficacy of exclusive enteral nutrition to induce remission in children (and recently adults) with Crohn's disease has totally changed the clinical practice. Food components that have an anti-inflammatory role on the intestine (vitamin D, butyrate, resveratrol, curcumin) may now serve as an adjuvant to treatment. While our understanding has expanded in recent years, there remain many aspects of the interactions between nutrition and the gut that remain to be elucidated. Further focused research may lead to advances in understanding of disease pathogenesis and also result in new improved therapeutic interventions.

Stable isotope ratios of carbon, nitrogen and selenium concentration in the scalp hair of Crohn's disease patients who ingested the elemental diet Elental®.

RATIONALE: Elental® is an elemental diet widely used as a nutritional supplement for Crohn's disease (CD) patients in Japan. Elental® contains amino acids as nitrogen sources and does not contain selenium (Se), and the δ13 C and δ15 N values of Elental® are markedly higher and lower, respectively, than those of a normal diet. METHODS: We compared the δ13 C and δ15 N values and Se concentration in the scalp hair of CD patients with those of control subjects who ate a regular diet, and estimated the amount of Elental® ingested as a supplement. The δ13 C and δ15 N values and the Se concentrations were quantified using isotope ratio mass spectrometry (IRMS) and inductively coupled plasma mass spectrometry (ICP-MS), respectively. RESULTS: An increase in Elental® ingestion increased the δ13 C value in the hair of CD patients (p <0.05), while it reduced the δ15 N value (p <0.05) and tended to reduce the Se concentration in female patients. CONCLUSIONS: The amount of Elental® ingested could be estimated by the δ13 C and δ15 N values in the hair of CD patients. Furthermore, the Se deficiency in female patients may be predicted from the δ13 C and δ15 N values.

Dietary interventions for induction and maintenance of remission in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD), comprised of Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic mucosal inflammation, frequent hospitalizations, adverse health economics, and compromised quality of life. Diet has been hypothesised to influence IBD activity. OBJECTIVES: To evaluate the efficacy and safety of dietary interventions on IBD outcomes. SEARCH METHODS: We searched the Cochrane IBD Group Specialized Register, CENTRAL, MEDLINE, Embase, Web of Science, Clinicaltrials.gov and the WHO ICTRP from inception to 31 January 2019. We also scanned reference lists of included studies, relevant reviews and guidelines. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared the effects of dietary manipulations to other diets in participants with IBD. Studies that exclusively focused on enteral nutrition, oral nutrient supplementation, medical foods, probiotics, and parenteral nutrition were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, extracted data and assessed bias using the risk of bias tool. We conducted meta-analyses where possible using a random-effects model and calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes. We assessed the certainty of evidence using GRADE. MAIN RESULTS: The review included 18 RCTs with 1878 participants. The studies assessed different dietary interventions for active CD (six studies), inactive CD (seven studies), active UC (one study) and inactive UC (four studies). Dietary interventions involved either the consumption of low amounts or complete exclusion of one or more food groups known to trigger IBD symptoms. There was limited scope for data pooling as the interventions and control diets were diverse. The studies were mostly inadequately powered. Fourteen studies were rated as high risk of bias. The other studies were rated as unclear risk of bias.The effect of high fiber, low refined carbohydrates, low microparticle diet, low calcium diet, symptoms-guided diet and highly restricted organic diet on clinical remission in active CD is uncertain. At 4 weeks, remission was induced in: 100% (4/4) of participants in the low refined carbohydrates diet group compared to 0% (0/3) of participants in the control group (RR 7.20, 95% CI 0.53 to 97.83; 7 participants; 1 study; very low certainty evidence). At 16 weeks, 44% (23/52) of participants in the low microparticle diet achieved clinical remission compared to 25% (13/51) of control-group participants (RR 3.13, 95% CI 0.22 to 43.84; 103 participants; 2 studies; I² = 73%; very low certainty evidence). Fifty per cent (16/32) of participants in the symptoms-guided diet group achieved clinical remission compared to 0% (0/19) of control group participants (RR 20.00, 95% CI 1.27 to 315.40; 51 participants ; 1 study; very low certainty evidence) (follow-up unclear). At 24 weeks, 50% (4/8) of participants in the highly restricted organic diet achieved clinical remission compared to 50% (5/10) of participants in the control group (RR 1.00, 95% CI 0.39 to 2.53; 18 participants; 1 study; very low certainty evidence). At 16 weeks, 37% (16/43) participants following a low calcium diet achieved clinical remission compared to 30% (12/40) in the control group (RR 1.24, 95% CI 0.67 to 2.29; 83 participants; 1 study; very low certainty evidence).The effect of low refined carbohydrate diets, symptoms-guided diets and low red processed meat diets on relapse in inactive CD is uncertain. At 12 to 24 months, 67% (176/264) of participants in low refined carbohydrate diet relapsed compared to 64% (193/303) in the control group (RR 1.04, 95% CI 0.87 to 1.25; 567 participants; 3 studies; I² = 35%; low certainty evidence). At 6 to 24 months, 48% (24/50) of participants in the symptoms-guided diet group relapsed compared to 83% (40/48) participants in the control diet (RR 0.53, 95% CI 0.28 to 1.01; 98 participants ; 2 studies; I² = 54%; low certainty evidence). At 48 weeks, 66% (63/96) of participants in the low red and processed meat diet group relapsed compared to 63% (75/118) of the control group (RR 1.03, 95% CI 0.85 to 1.26; 214 participants; 1 study; low certainty evidence). At 12 months, 0% (0/16) of participants on an exclusion diet comprised of low disaccharides / grains / saturated fats / red and processed meat experienced clinical relapse compared to 26% (10/38) of participants on a control group (RR 0.11, 95% CI 0.01 to 1.76; 54 participants; 1 study; very low certainty evidence).The effect of a symptoms-guided diet on clinical remission in active UC is uncertain. At six weeks, 36% (4/11) of symptoms-guided diet participants achieved remission compared to 0% (0/10) of usual diet participants (RR 8.25, 95% CI 0.50 to 136.33; 21 participants; 1 study; very low certainty evidence).The effect of the Alberta-based anti-inflammatory diet, the Carrageenan-free diet or milk-free diet on relapse rates in inactive UC is uncertain. At 6 months, 36% (5/14) of participants in the Alberta-based anti-inflammatory diet group relapsed compared to 29% (4/14) of participants in the control group (RR 1.25, 95% CI 0.42 to 3.70; 28 participants; 1 study; very low certainty evidence). Thirty per cent (3/10) of participants following the carrageenan-free diet for 12 months relapsed compared to 60% (3/5) of the participants in the control group (RR 0.50, 95% CI 0.15 to 1.64; 15 participants; 1 study; very low certainty evidence). At 12 months, 59% (23/39) of milk free diet participants relapsed compared to 68% (26/38) of control diet participants (RR 0.83, 95% CI 0.60 to 1.15; 77 participants; 2 studies; I² = 0%; low certainty evidence).None of the included studies reported on diet-related adverse events. AUTHORS' CONCLUSIONS: The effects of dietary interventions on CD and UC are uncertain. Thus no firm conclusions regarding the benefits and harms of dietary interventions in CD and UC can be drawn. There is need for consensus on the composition of dietary interventions in IBD and more RCTs are required to evaluate these interventions. Currently, there are at least five ongoing studies (estimated enrollment of 498 participants). This review will be updated when the results of these studies are available.